Streptococcus pneumoniae Pneumonia in Mice: Optimal Amoxicillin Dosing Predicted from a Pharmacokinetic- Pharmacodynamic Model

In an attempt to better understand the interaction of amoxicillin with Streptococcus pneumoniae in the lung, and to determine the parameters of therapeutic efficacy of the antimicrobial agent amoxicillin, we used a pharmacokinetic-pharmacody-namic model to describe the overall dose-effect relationship of amoxicillin against 12 strains of S. pneumoniae with penicillin minimum inhibitory concentrations ranging from,0.01 to 16 mg/ml in a neutropenic murine pneumonia model. We were able to correlate amoxicillin dosing, pharmacokinetics, and the tem-poral changes in bacterial count in lung. Moreover, survival rates measured in one strain at different dosing were signifi-cantly related to the number of bacteria in lung calculated from the pharmacokinetic-pharmacodynamic model. Disappearance of amoxicillin from the effect compartment appeared to be ver